Proteolytic Cleavage of Apolipoprotein E in the Down Syndrome Brain

Down syndrome (DS) is one of the most common genetic causes of intellectual disability and is characterized by a number of behavioral as well as cognitive symptoms. Many of the neuropathological features of early-onset Alzheimer’s disease (AD) including senile plaques and neurofibrillary tangles (NFTs) are also present in people with DS as a result of triplication of the amyloid precursor gene on chromosome 21. Evidence suggests that harboring one or both apolipoprotein E4 (APOE4) alleles may increase the risk for AD due to the proteolytic cleavage of apoE4 and a subsequent loss of function. To investigate a role for the apoE proteolysis in vivo, we compared three autopsy groups; 7 DS with AD neuropathology cases over 40 years, 5 young DS cases without AD pathology under 40 years (YDS) and 5 age-matched control cases over 40 years by immunohistochemistry utilizing an antibody that detects the amino-terminal fragment of apoE. Application of this antibody, termed the amino-terminal apoE fragment antibody (nApoECF) revealed labeling of pyramidal neurons in the frontal cortex of YDS cases, whereas in the DS-AD group, labeling with nApoECF was prominent within NFTs. NFT labeling with nApoECF was significantly greater in the hippocampus versus the frontal cortex in the same DS-AD cases, suggesting a regional distribution of truncated apoE. Colocalization immunofluorescence experiments indicated that 52.5% and 53.2% of AT8- and PHF-1-positive NFTs, respectively, also contained nApoECF. Collectively, these data support a role for the proteolytic cleavage of apoE in DS and suggest that apoE fragmentation is closely associated with NFTs

Does Diet Affect Growth in Juvenile Lingcod?

CERM Poster 2009. To determine if diet affects the growth rate of juvenile ling cod, we began with three initial objectives: 1) Record the growth rates of juvenile lingcod on different diets (squid and sardine); 2) Determine if hemocyanin will cause lingcod skin and muscle pigmentation will take on a blue/green pigmentation; and 3) Observe the acclimation process as the juvenile lingcod adjust to an artificial environment. Our initial results showed no significant differences in growth rate. Further research will focus on seeing if diet can affect color of our fish from controlled tank one (sardine) and experimental tank two (squid)diets. We are hypothesizing that the hemocyanin in the squid blood will result in our fish turning blue-green. Outcomes will assessed using a comparison of post-treatment sampling photos with baseline photos taken at start of experiment.This poster was the result of a student research project for the Fall 2009 FW 426/526, Coastal Ecology and Resource Management. It was presented December 9, 2009 at the Hatfield Marine Science Center.KEYWORDS: Diet, Growth rates, Lingcod, Hatfield Marine Science Center, Ophiodon elongatu

Distribution of Microglial Phenotypes as a Function of Age and Alzheimer\u27s Disease Neuropathology in the Brains of People with Down Syndrome

Introduction: Microglial cells play an important role in the development of Alzheimer\u27s disease (AD). People with Down syndrome (DS) inevitably develop AD neuropathology (DSAD) by 40 years of age. We characterized the distribution of different microglial phenotypes in the brains of people with DS and DSAD. Methods: Autopsy tissue from the posterior cingulate cortex (PCC) from people with DS, DSAD, and neurotypical controls was immunostained with the microglial marker Iba1 to assess five microglia morphological types. Results: Individuals with DS have more hypertrophic microglial cells in their white matter. In the gray matter, individuals with DSAD had significantly fewer ramified microglia and more dystrophic microglia than controls and the younger individuals with DS. The DSAD group also exhibited more rod-shaped and amoeboid cells than the AD group. Discussion: Individuals with DS and DSAD show a microglial phenotype that distinguishes them from non-DS controls

Down Syndrome: Age-Dependence of PiB Binding in Postmortem Frontal Cortex Across the Lifespan

Beta-amyloid (Aβ) deposition in brain accumulates as a function of age in people with Down syndrome (DS) with subsequent development into Alzheimer disease neuropathology, typically by 40 years of age. In vivo imaging using the Pittsburgh Compound B (PiB) ligand has facilitated studies linking Aβ, cognition, and dementia in DS. However, there are no studies of PiB binding across the lifespan in DS. The current study describes in vitro 3H-PiB binding in the frontal cortex of autopsy cases with DS compared to non-DS controls. Tissue from 64 cases included controls (N=25) and DS (N=39). In DS, 3H-PiB binding was significantly associated with age. After age 40 years in DS, 3H-PiB binding rose dramatically along with increasing individual variability. 3H-PiB binding correlated with the amount of Aβ42. Using fixed frontal tissue and fluorescent 6-CN-PiB, neuritic and cored plaques along with extensive cerebral amyloid angiopathy (CAA) showed 6-CN-PiB binding. These results suggest that cortical PiB binding as shown by positron emission tomography imaging reflects plaques and CAA in DS brain

Quantitative Bias in Illumina TruSeq and a Novel Post Amplification Barcoding Strategy for Multiplexed DNA and Small RNA Deep Sequencing

Here we demonstrate a method for unbiased multiplexed deep sequencing of RNA and DNA libraries using a novel, efficient and adaptable barcoding strategy called Post Amplification Ligation-Mediated (PALM). PALM barcoding is performed as the very last step of library preparation, eliminating a potential barcode-induced bias and allowing the flexibility to synthesize as many barcodes as needed. We sequenced PALM barcoded micro RNA (miRNA) and DNA reference samples and evaluated the quantitative barcode-induced bias in comparison to the same reference samples prepared using the Illumina TruSeq barcoding strategy. The Illumina TruSeq small RNA strategy introduces the barcode during the PCR step using differentially barcoded primers, while the TruSeq DNA strategy introduces the barcode before the PCR step by ligation of differentially barcoded adaptors. Results show virtually no bias between the differentially barcoded miRNA and DNA samples, both for the PALM and the TruSeq sample preparation methods. We also multiplexed miRNA reference samples using a pre-PCR barcode ligation. This barcoding strategy results in significant bias

Central Coherence in Eating Disorders: A Synthesis of Studies Using the Rey Osterrieth Complex Figure Test

Background: Large variability in tests and differences in scoring systems used to study central coherence in eating disorders may lead to different interpretations, inconsistent findings and between study discrepancies. This study aimed to address inconsistencies by collating data from several studies from the same research group that used the Rey Osterrieth Complex Figure Test (Rey Figure) in order to produce norms to provide benchmark data for future studies. Method: Data was collated from 984 participants in total. Anorexia Nervosa, Bulimia Nervosa, recovered Anorexia Nervosa, unaffected family members and healthy controls were compared using the Rey Figure. Results: Poor global processing was observed across all current eating disorder sub-groups and in unaffected relatives. There was no difference in performance between recovered AN and HC groups. Conclusions: This is the largest dataset reported in the literature and supports previous studies implicating poor global processing across eating disorders using the Rey Figure. It provides robust normative data useful for future studies

Protocol for north of England and Scotland study of tonsillectomy and adeno-tonsillectomy in children (NESSTAC). A pragmatic randomised controlled trial comparing surgical intervention with conventional medical treatment in children with recurrent sore throats

BACKGROUND: Uncertainties surrounding the effectiveness and cost-effectiveness of childhood tonsillectomy for recurrent sore throat led the NHS Health Technology Assessment Programme to commission this research to evaluate the effectiveness and cost-effectiveness of tonsillectomy and adeno-tonsillectomy in comparison with standard non-surgical management in children aged under 16 with recurrent throat infections. The aim is to evaluate if tonsillectomy and adeno-tonsillectomy reduces the number of episodes of sore throats among children to a clinically significant extent. METHODS/DESIGN: A simple prospective pragmatic randomised controlled trial with economic analysis and prospective cohort study of non-trial participants comparing surgical intervention with conventional medical treatment. The treatment arm will receive tonsillectomy and adeno-tonsillectomy while in the control arm non-surgical conventional medical treatment only will be used. The primary outcome measure will be reported number of episodes of sore throat over two years with secondary outcomes measures of reported number of episodes of sore throat, otitis media and upper respiratory tract infection which invoke a GP consultation; reported number of symptom-free days; reported severity of sore throats and surgical and anaesthetic morbidity. The study will take place in five hospitals in the UK. The trial population will be 406 children aged 4–15 on their last birthday with recurrent sore throat referred by primary care to the 5 otolaryngology departments. The duration of the study is seven years (July 2001- July 2008). DISCUSSION: As with all pragmatic randomised controlled trials it is impossible to control the external environment in which the research is taking place. Since this trial began a number of factors have arisen which could affect the outcome including; a reduction in the incidence of respiratory tract infections, marked socio-economic differences in consultation rates, the results from the National Prospective Tonsillectomy Audit and the Government's waiting list initiatives

Do Children and Adolescents with Anorexia Nervosa Display an Inefficient Cognitive Processing Style?

Objective: This study aimed to examine neuropsychological processing in children and adolescents with Anorexia Nervosa (AN). The relationship of clinical and demographic variables to neuropsychological functioning within the AN group was also explored.  Method: The performance of 41 children and adolescents with a diagnosis of AN were compared to 43 healthy control (HC) participants on a number of neuropsychological measures.  Results: There were no differences in IQ between AN and HC groups. However, children and adolescents with AN displayed significantly more perseverative errors on the Wisconsin Card Sorting Test, and lower Style and Central Coherence scores on the Rey Osterrieth Complex Figure Test relative to HCs.  Conclusion: Inefficient cognitive processing in the AN group was independent of clinical and demographic variables, suggesting it might represent an underlying trait for AN. The implications of these findings are discussed